《Table 1Effects of bergapten on transport of vincristine sulfate in MDCK-MDR1 cell (mean±SD, n=3) .》

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《Mechanism underlying bergapten-mediated regulation of vincristine transport in MDCK-MDR1 cells》

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Compared with vincristine 244.1μg/mL，*P<0.05，**P<0.01.

Angelica dahurica（Fisch.ex Hoffm.）Benth.et Hook.f is used as a common herb in prescriptions such as Yuanhu Zhitong Tablets，Duliang Pills，and Tongqiao Biyan Tablets，which are collected in the Chinese Pharmacopoeia.A.dahurica exerts a protective effect against different forms of pain（Wu，Jiang，Ma，&Gao，2009）.Coumarins and volatile oils are the main active components of A.dahurica（Zhu，Li，Ma，&Liu，2014）.Our previous study showed that coumarins of A.dahurica could increase the intestinal absorption of drugs，such as puerarin and baicalin（Liang et al.，2012；Liao et al.，2014；Zhao et al，2012；Zhu et al.，2013），by decreasing the expression of P-gp（Liang et al.，2015）.To date，55 coumarin compounds have been obtained from A.dahurica，which contains the compounds imperalorin，isoimperalorin，oxypeucedanin，byakangelicin，and bergapten in higher amounts（Wei，Xu，Yang，&He，2016；Zhang et al.，2015；Zhao et al.，2015）.However，the identity of the coumarin that can improve the intestinal transport of other drugs is unknown.Therefore，to identify the monomer compositions which can improve the intestinal absorption of other drugs，we studied the effects of each of these individual coumarins on intestinal absorption function and explore the underlying mechanisms.In this study，we first investigated the effect of bergapten on the intestinal transport of vincristine sulfate，which is affected by P-gp.Then，based on the efflux transporter function and membrane fluidity，we studied the possible mechanism of action of bergapten.In modern pharmaceutical studies，bergapten，one of the major bioactive constituents of A.dahurica，has been reported to have important biological activities，including exerting effects against hypertension，HIV，cancer，and bacteria（Kostova&Momekov，2006；Xu，Xu，&Li，2000）.To date，few studies have investigated how these functions affect the intestinal absorption of other drugs.